Human lymphocytes, upon activation, express on their cell surfaces a number of new receptors for cytokines. The cascade of early appearing activation antigens include receptors for: IL-2, transferrin, insulin, IL-4, and insulin-like growth factors types I and II. The effects of these cytokines on their own and other cytokine receptors is being studied through radioligand binding, receptor enumeration by Scatchard analysis, receptor structure identified by chemical crosslinking of iodinated ligand-receptor complexes and the level of receptor messenger RNA induction by Northern blot analysis. IL-4 and IL-2 along with other immunomodulators are being examined for their mechanism of enhancement or suppression of cell-mediated immune responses by assessing their effects on growth factor production and receptor expression. Delineating the events that occur during lymphocyte activation and understanding the consequences of perturbing these events, should help us pinpoint defects in regulation of cellmediated immunity and provide a model for analyzing the effects of other cytokines on the immune response. In addition, we are also studying the IL-2 receptor as a target for immunotherapy. Therapeutic reagents being studied include toxin-conjugated IL-2 and anti-IL-2 receptor monoclonal antibodies along with radionuclide (alpha and beta particle emitters) chelate coupled anti-IL-2 receptor monoclonal antibodies. The design of cytokine-toxin recombinant fusion proteins along with cytolytic conjugates of MAb are tested for specificity, stability and toxicity in animal models for evaluation as potential therapeutic reagents for human use in treatment of cancer, transplantation and autoimmune diseases.